Optical vector analyzer with time-domain analysis capability.

Time-domain analysis (TDA) is useful for measuring optical devices along with a link and for diagnosing a long device. In this Letter, an optical vector analyzer with TDA capability is proposed and experimentally demonstrated. The key to realizing TDA is a low-coherence optical carrier, which is achieved by modulating an electrical broadband signal on a continuous-wave light via acousto-optic modulation. Then, optical single-sideband modulation and vector balanced detection are used to measure the total frequency response of multiple devices under test (DUTs). Through an inverse Fourier transform, the obtained DUT impulses are distinguished in the time domain. Finally, time-domain gating and Fourier transform are applied to extract the frequency response of each DUT. An experiment is performed in which a fiber link comprising three DUTs and an H 13 C 14 N gas cell with a breakpoint inserted is characterized. The frequency setting resolution is 5 MHz, and a time-domain resolution of 30.84 ns is proved, which can reach 14.881 ns in theory.

Comprehensive vector analysis for electro-optical, opto-electronic, and optical devices.

High-performance electro-optical (E-O), opto-electronic (O-E), and optical (O-O) devices are widely used in optical communications, microwave photonics, fiber sensors, and so on. Measurement of the amplitude and phase responses are essential for the development and fabrication of these devices. However, the previous methods can hardly characterize the E-O, O-E, and O-O devices with arbitrary responses. Here we propose a comprehensive vector analyzer based on optical asymmetrical double-sideband (ADSB) modulation to overcome this difficulty. The ADSB solves the problem of frequency aliasing and can extract information from both the +1st- and -1st-order sidebands. Thus, most devices in photonic applications, including phase modulators, can be characterized. In the experiment, a commercial photodetector, a phase modulator, and a sampled FBG are used as the O-E, E-O, and O-O devices under test, respectively. A frequency resolution of 2 MHz, an electrical sweeping range of 40 GHz, and an optical sweeping range of 80 GHz are achieved.

Signal transducer and activator of transcription 3 inhibition enhances vemurafenib sensitivity in colon cancers harboring the BRAFV600E mutation.

The BRAFV600E inhibitor vemurafenib is widely used to treat melanomas harboring the activated BRAFV600E mutation; however, vemurafenib showed poor efficacy in colon cancer, which impeded its clinical application for colon cancer patients with this mutation. The specific mechanism of vemurafenib resistance is not clear in colon cancer. In this study, we demonstrated that signal transducer and activator of transcription 3 (STAT3) activation influenced vemurafenib sensitivity in BRAFV600E mutant colon cancer cells. When vemurafenib was applied to two colon cancer cell lines with the BRAFV600E mutation, STAT3 was continuously activated after 6 hours. Furthermore, BCL-2 was upregulated in RKO colon cancer cells, while STAT3 remained unchanged in HT-29 colon cancer cells. This suggested that STAT3 signaling might be involved in vemurafenib sensitivity. Combining the STAT3 inhibitor STATTIC with vemurafenib further inhibited cell proliferation and promoted apoptosis by downregulating STAT3 and BCL-2 expression in RKO cells. Further studies showed that interleukin 6 (IL-6) secretion increased after RKO cells were treated with vemurafenib. STAT3 activation was induced by adding IL-6 to the supernatant, and IL-6 increased STAT3 and BCL-2 expression and antagonized vemurafenib sensitivity in HT-29 cells. Together, these results suggest that STAT3 activation maybe related to vemurafenib sensitivity in colon cancer cells, and that combining STAT3 inhibitors with vemurafenib may be a promising treatment for BRAFV600E mutant colon cancers.

Treatment-related serious adverse events and fatal adverse events with regorafenib in cancer patients: a meta-analysis of phase 3 randomized controlled trials.

Regorafenib (Stivarga) is an oral small-molecule multikinase inhibitor commonly used against a variety of cancers. We performed a meta-analysis of all phase 3 randomized controlled trials (RCTs) of regorafenib to quantify the increased risk of SAEs and FAEs. We carried out a systematic search of electronic databases for studies published from inception to February 2017 without any restrictions. Eligibility criteria included phase 3 RCTs of tumors comparing regorafenib, alone or in combination with non-targeted chemotherapy (regorafenib arm) versus placebo or non-targeted chemotherapy (control arm). Data on SAEs and FAEs were extracted from each study and pooled to determine the overall incidence, relative risks (RRs) and 95% confidence intervals (CIs). A total of four phase 3 RCTs involving 1736 cancer patients met the eligibility criteria and were included. The overall incidence of SAEs and FAEs with regorafenib were 0.23 (95%CI, 0.05-0.40) and 0.02 (95%CI, 0.01-0.03), respectively. Compared with control, the summary RR of developing a regorafenib-related SAE was 1.60 (95%CI, 0.95-2.68, P=0.07), the summary RR of developing a regorafenib-related FAE was 1.71 (95%CI, 0.69-4.24, P=0.25). No evidence was found for the association between regorafenib and higher risk of SAEs and FAEs. This association varied significantly with cancer types (P=0.02) for SAEs but no evidence of heterogeneity was found for FAEs. This meta-analysis demonstrates no evidence for the association between regorafenib and higher risk of SAEs and FAEs. This analysis will be important when considering the trade-off of regorafenib treatment during clinical decision-making.

Score for Predicting Active Cancer in Patients with Ischemic Stroke: A Retrospective Study.

BACKGROUND: We aimed to examine the differences of clinical characteristics between patients with ischemic stroke with active cancer and those without cancer to develop a clinical score for predicting the presence of occult cancer in patients with ischemic stroke. METHODS: This retrospective study enrolled consecutive adult patients with acute ischemic stroke who were admitted to our department between December 2017 and January 2019. The demographic, clinical, laboratory, and neuroimaging characteristics were compared between patients with ischemic stroke with active cancer and those without cancer. Multivariate analysis was performed to identify independent factors associated with active cancer. Subsequently, a predictive score was developed using the areas under the receiver operating characteristic curves based on these independent factors. Finally, Bayesian decision theory was applied to calculate the posterior probability of active cancer for finding the best scoring system. RESULTS: Fifty-three (6.63%) of 799 patients with ischemic stroke had active cancer. The absence of a history of hyperlipidemia (odds ratio (OR) = 0.17, 95% confidence interval (CI): 0.06-0.48, P < 0.01), elevated serum fibrinogen (OR = 1.72, 95% CI: 1.33-2.22, P < 0.01) and D-dimer levels (OR = 1.43, 95% CI: 1.24-1.64, P <0.01), and stroke of undetermined etiology (OR = 22.87, 95% CI: 9.91-52.78, P < 0.01) were independently associated with active cancer. A clinical score based on the absence of hyperlipidemia, serum fibrinogen level of ≥4.00 g/L, and D-dimer level of ≥2.00 µg/mL predicted active cancer with an area under the curve of 0.83 (95% CI: 0.77-0.89, P < 0.01). The probability of active cancer was 59% at a supposed prevalence of 6.63%, if all three independent factors were present in a patient with ischemic stroke. CONCLUSIONS: We devised a clinical score to predict active cancer in patients with ischemic stroke based on the absence of a history of hyperlipidemia and elevated serum D-dimer and fibrinogen levels. The use of this score may allow for early intervention. Further research is needed to confirm the implementation of this score in clinical settings.

Comparison of efficacy and safety for patients with beyond second line treated metastatic colorectal cancer: a network meta-analysis of randomized controlled trials.

Patients with metastatic colorectal cancer (mCRC) beyond second line treatment have a poor prognosis. Regorafenib, TAS-102, fruquintinib, panitumumab and cetuximab are recommended single-agent chemotherapy regimens for patients exhibiting disease progression, this meta-analysis aimed to evaluate the efficacy and safety of these regimens in randomized controlled trials (RCTs). Eight RCTs with 3,832 cancer patients were included. Results showed that there was no significant difference in OS and PFS among the four drugs when comparing all patients or patients who have the KRAS gene mutation. In patients with wild-type KRAS, the four drugs exhibited significantly better OS and PFS than the placebo group, with the exception of OS with panitumumab treatment. Fruquintinib exhibited better PFS, good tolerability and reduced gastrointestinal adverse effects in wild-type KRAS subgroup, making it a promising agent to treat patients with wild-type KRAS mCRC beyond the second line.